| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 10 mM * 1 mL in DMSO |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| 靶点 |
ERK1 (IC50 = 6.1 nM); ERK2 (IC50 = 3.1 nM); p-RSK (IC50 = 12 nM)
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|---|---|
| 体外研究 (In Vitro) |
Ravoxertinib (GDC-0994) 还抑制 p90RSK，IC50 为 12 nM[1]。 Ravoxertinib (GDC-0994) 的生化效价分别为 1.1 nM 和 0.3 nM，对 ERK1 和 ERK2 具有高度选择性[2]。 Ravoxertinib（GDC0994；50 nM、0.5 µM 和 5 µM；48 小时）会降低肺腺癌细胞系（A549、HCC827 和 HCC4006）的活力[3]。
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| 体内研究 (In Vivo) |
在 CD-1 小鼠中，口服 10 mg/kg 剂量的 Ravoxertinib (GDC-0994) 足以在 CD-1 小鼠中提供所需的靶标覆盖至少 8 小时[1]。每天口服时，Ravoxertinib 在多种体内癌症模型中表现出显着的单药活性，包括小鼠中的 KRAS 和 BRAF 突变人类异种移植肿瘤[2]。
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| 酶活实验 |
Ravoxertinib (GDC-0994) 是一种口服生物可利用的 ERK 激酶抑制剂，对于 ERK1 和 ERK2 的 IC50 分别为 6.1 nM 和 3.1 nM。此外，p90RSK 被 ravoxertinib (GDC-0994) 抑制，IC50 为 12 nM。 ravoxertinib (GDC-0994) 的生化效力分别为 1.1 nM 和 0.3 nM，对 ERK1 和 ERK2 具有高度选择性。
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| 细胞实验 |
GDC-0994 有效抑制肿瘤细胞中的磷酸化 p90RSK。
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| 动物实验 |
Mice: PK/PD data for the mouse xenograft HCT116 model of ravoxertinib (GDC-0994). In nude mice, 400–600 mm3 of tumor volume is reached by HCT116 tumors. Tumor and plasma samples are collected 2, 8, 16, and 24 hours after the initial oral dose of 22 at 15, 30, or 100 mg/kg for mice versus the vehicle control alone (40% PEG400/60% (10% HPβCD)). Quantitative Western blotting is used to assess the relative levels of total p90RSK (tRSK) and phosphorylated p90RSK (pRSK) in tumors. At 2 hours after the dose, these levels are normalized to the vehicle control (set to 100%). LC-MS is used to determine the concentrations in plasma and tumors.
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| 参考文献 |
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| 分子式 |
C21H18CLFN6O2
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|---|---|
| 分子量 |
439.85
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| 精确质量 |
440.12
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| 元素分析 |
C, 57.21; H, 4.12; Cl, 8.04; F, 4.31; N, 19.06; O, 7.26
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| CAS号 |
1453848-26-4
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| 相关CAS号 |
Ravoxertinib hydrochloride;2070009-58-2
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| 外观&性状 |
Solid powder
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| SMILES |
CN1C(=CC=N1)NC2=NC=CC(=N2)C3=CC(=O)N(C=C3)[C@H](CO)C4=CC(=C(C=C4)Cl)F
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| InChi Key |
RZUOCXOYPYGSKL-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C21H18ClFN6O2/c1-28-19(5-8-25-28)27-21-24-7-4-17(26-21)13-6-9-29(20(31)11-13)18(12-30)14-2-3-15(22)16(23)10-14/h2-11,18,30H,12H2,1H3,(H,24,26,27)/t18-/m1/s1
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| 化学名 |
1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]pyridin-2-one;hydrochloride
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| 别名 |
RG7842; GDC-0994; RG 7842; GDC 0994; GDC0994; RG-7842
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外) |
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|---|---|---|---|---|
| 溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.67 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (3.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 1.67 mg/mL (3.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 5: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 30mg/mL Solubility in Formulation 6: 5 mg/mL (11.34 mM) in 30% PEG300 70% (10% HP-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2735 mL | 11.3675 mL | 22.7350 mL | |
| 5 mM | 0.4547 mL | 2.2735 mL | 4.5470 mL | |
| 10 mM | 0.2274 mL | 1.1368 mL | 2.2735 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
UV traces from incubation of6with hepatocytes att= 3 h (M3 = compound7): h = human, m = mouse, r = rat, d = dog, c = cynomolgus monkey.
Compound exposure vs time in a multidose mouse PK study with compound22, formulated in 40% PEG400/60% (10% HPβCD) water.J Med Chem.2016 Jun 23;59(12):5650-60. |
Crystal structures of22bound to ERK2 (brown) and CDK2 (purple): (A) compound22bound to ERK2; (B) superposition of ERK2 and CDK2 cocrystal structures with compound22. Red dotted lines indicate hydrogen bonds. Red spheres indicate water molecules.
HCT116 study PK/PD analysis with compound22: PK/PD data for22in the HCT116 mouse xenograft model.J Med Chem.2016 Jun 23;59(12):5650-60. |
Activity of22against 279 kinases at 1 μM. Illustration reproduced courtesy of Cell Signaling Technology.
HCT116 mouse xenograft data with compound22.J Med Chem.2016 Jun 23;59(12):5650-60. |
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